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June 19, 2008

Once Fatal, Some Cancers Are Now Chronic

by Sam Savage

By Jane E. Brody

To see Barry Cooper working out at the YMCA in Brooklyn, New York, every morning before going to work as a patent lawyer, you would be unlikely to guess that he has cancer. Cooper, 63 and a grandfather of two, is one of a small but growing number of patients for whom once-fatal cancer has become a chronic disease.

Through a better understanding of factors that distinguish cancer cells from normal ones and the development of more specific treatments that capitalize on those differences, cancers that just a decade ago would have been rapidly fatal are now being controlled for years while the patients conduct near-normal lives.

Although these cancers may never be curable, they can often be controlled for long periods by a succession of treatments. When one therapeutic approach no longer works, another one that has come along in the meantime might stop the disease from progressing, at least for a while.

Even patients whose cancers were already metastatic - spread beyond the site of origin - at the time of diagnosis are benefiting from this sequential approach. Others like Cooper have cancers of blood-forming organs that previously had a limited response to available therapies.

"We're seeing people being periodically treated and living year after year with advanced disease, with cancers that have spread to the lung, liver, brain or bone," Dr. Michael Fisch, director of the general oncology program at the M.D. Anderson Cancer Center in Houston, said in an interview. "In 1997, we wouldn't have guessed this would be possible."

In March 2007, Elizabeth Edwards, wife of former presidential hopeful John Edwards, joined this group of chronic cancer patients when she disclosed that the breast cancer she was treated for in 2004 had spread to her bones and, possibly, lung. Edwards described the disease as "no longer curable but completely treatable" and likened the situation to living with diabetes.

Speaking generally, Dr. Francisco Esteva, a breast cancer specialist at the Anderson center, said in an interview: "Our ultimate goal is not to make this a chronic disease, but to keep patients alive long enough until we can find the right treatment for the right patient and cure the disease. Unfortunately, we're not there yet, but meanwhile we try to keep patients alive with a good quality of life for as long as possible."

Fisch calls the new therapy for advanced cancer "the hitchhiker model."

Time is bought by going from point A, the first-line therapy, to point B, the second-line therapy, to point C, the third line of therapy, and so on. The approach can continue indefinitely, as long as new therapies become available and patients remain well enough to withstand the rigors of treatment.

But Fisch noted that adding meaningful years to the lives of patients with advanced cancer depends in part on avoiding the attitude, prevalent among some physicians, that cancer is hopeless after it has metastasized.

In December 2005, at age 61, Cooper seemed hale and hearty, though he was unusually tired. Then a routine checkup resulted in a shocking diagnosis - chronic myelogenous leukemia, commonly called CML. "My initial disbelief was followed by varying degrees of anger and denial," Cooper said. "I found it very difficult to accept my diagnosis."

His doctor reassured him that he was lucky. His disease, once a gradually progressive killer, was still in a chronic stage and of a type, Philadelphia positive, that could now be controlled by a drug, Gleevec, licensed just a year earlier. And if and when Gleevec, taken daily by mouth, no longer worked or caused intolerable side effects, the doctor told him, other drugs were in the pipeline that could take over.

Cooper lost no time from work, and Gleevec kept his cancer's runaway white blood cells in check for more than two years. When he developed resistance to it, he switched to a second-generation drug.

"For a majority of people with CML," Cooper said, "Gleevec is a wonder drug, making the disease something like diabetes - controllable even if not curable."

Although he said not a day went by when he did not think about his cancer, he and his wife, Naomi, are letting no grass grow under their feet. Since the diagnosis, they have traveled abroad several times, they visit their grandchildren often and celebrated their 40th anniversary with a lavish party that Cooper described as "a very life-affirming event."

Max Watson, who has multiple myeloma, a usually deadly blood system cancer, has been able to control his disease for six years through the hitchhiker approach. His succession of treatments has included stem cell transplants, radiation and drug therapies. When one treatment failed, another became available.

Although at first Watson did not think long-term survival was possible, he was quoted in OncoLog, an M.D. Anderson report to physicians, as saying, "Eventually, I realized that this was something I would be dealing with for a long time."

As Elizabeth Edwards's prospects show, some solid tumors in advanced stages are also behaving more like chronic diseases, a result of research that has discovered molecular characteristics of specific cancers and the development of drugs that take advantage of a cancer's Achilles' heel.

Esteva described a breast cancer patient first treated with a mastectomy and the antiestrogen tamoxifen in 1995. Five years later, cancer had spread to her lungs, prompting treatment with a newer anticancer drug, an aromatase inhibitor. When that no longer worked, her cancer was found to possess a molecular factor, HER-2, and she began treatment with Herceptin, a designer drug tailor made to attack HER-2-positive breast cancer.

Herceptin therapy was able to stabilize her metastases for years, "something we had not seen before," Esteva said.

The patient now receives a combination of Herceptin and another drug and enjoys a relatively normal quality of life, the doctor reported.

There has also been progress in prolonging survival in patients with metastatic kidney cancer.

Dr. Nizar Tannir, a specialist in genitourinary cancer at the Houston center, said that before 2005 there was not much to offer patients with advanced renal cell carcinoma. But within two years, three new drugs became available that have resulted in a 50 percent increase in overall survival.

Tannir recommends that patients given a bleak prognosis seek a second opinion from an expert at a major cancer center, in person if possible, or by phone or e-mail through their doctor's office.